This proposal requests support for continuation of T32 MH016804 (Years 31-35). This highly successful T32 has traditionally trained individuals in both purely clinical and in translational neuroscience research. In this renewal application we have enhanced the emphasis of T32 MH016804 on translational neuroscience research training, so as to prepare the next generation of researchers to make discoveries that increase the variety and specificity of interventions to treat and prevent mental illness. Accordingly, we have re-titled our application Training for Transformative Discovery in Psychiatry. Our plan to emphasize training in studies engaged in forward and backward T1 translational research derives from our model for discovery in psychiatry (Fig 1). To support this goal, our training program has been augmented to ensure that: 1) Clinically trained individuals develop fluency in basic neuroscience knowledge; 2) Individuals with prior basic neuroscience training will receive exposures designed to help them develop fluency in the clinical, pathophysiologic, and pathologic manifestations of mental illness, and; 3) All participants receive training in translational strategies and techniques. Ultimately, trainees should acquire the ability to critically evaluate hypotheses and conduct experiments with knowledge of the clinical expression of mental illness, the associated cellular and molecular pathologies, the expected pathophysiologic mechanisms leading to the phenotype, and the possibilities and limitations of experimental models. Additional training focuses on professional skill development, the conduct of interdisciplinary research, and the responsible conduct of research. To achieve these training goals we have identified a new Director, Robert A. Sweet, M.D., chosen for his experience as a senior translational neuroscience investigator and his record of outstanding mentorship of translational neuroscience investigators. Dr. Sweet will be supported by the former Director, Charles F. Reynolds, III, M.D., an acclaimed mentor of clinical investigators whose ongoing engagement as Co-Director will also ensure programmatic continuity. They will be joined by new Co-Director, Etienne Sibille, Ph.D., who brings the perspective of a basic neuroscientist to the conduct of translational neuroscience studies of mental illness. We have similarly enhanced the training faculty by including new members with strong funding and training records in translational neuroscience, and by the inclusion of promising earlier career investigators who, through a co-mentorship model will be given the opportunity to develop as mentors. Combining the strong track record in the successful training of psychiatry researchers and mentors established during the past 30 years of success of T32 MH016804 with the guidance and emphasis on new discovery derived from the highly successful Translational Neuroscience Program at the University of Pittsburgh is anticipated to invigorate the Research Training Program supported by this application and promote the development of the next generation of translational neuroscience researchers and research mentors.